March 08, 2018
By Greg Peters
Researchers at the University of Kansas Medical Center are using a novel approach to monitor blood flow in the brain during exercise — a process that could help unlock the complex medical mysteries surrounding the importance of cerebrovascular health in brain aging, head injuries, stroke and Alzheimer's disease.
KU Medical Center scientists were the first researchers to publish a methodology for employing transcranial Doppler (TCD) ultrasound continuously during exercise to model cardiovascular blood flow response in the brain. By using TCD to map the blood flow response and the amplitude of the response in subjects from rest through the point where their heart rate levels out during moderate exercise, researchers can detect possible norms and patterns within specific test groups.
"We're really working hard to try to unlock some of the questions and provide new insights into how vascular risk may play a role in brain aging," said Sandra Billinger, Ph.D., PT, director the REACH Lab, who raised money for the TCD equipment by walking across Kansas in 2013. "With everything affecting brain health, and the fact that we're living longer, the global interest in trying to maintain brain health is an exciting avenue to pursue."
Billinger, who grew up in Hays and graduated from Thomas More Prep-Marian High School and Fort Hays State University, has coined the term "exercise stress test for the brain" to describe this new process of monitoring cerebral blood flow during moderate exercise. Basically for the test, subjects are fitted with an adjustable headband containing ultrasonic probes that are placed over the cranial temporal bone window while the individual exercises on a recumbent stepping machine. Participants sit quietly on the stepper and are instructed to start exercising until they reach a predetermined workload and their heart rates level out.
In a recently published paper, Billinger and her collaborators from the University of Kansas Alzheimer's Disease Center (KU ADC) were the first to show that people with normal thinking abilities but elevated amyloid in their brains had a blunted brain blood flow response during a single bout of exercise compared to those without elevated amyloid.
Billinger said she realized there was something unique about continuously monitoring the physical challenge of exercise thanks in part to a suggestion from Sarah Kwapiszeski, a former Doctor of Physical Therapy student in Billinger's lab. Kwapiszeski, who has since graduated, had been analyzing preliminary data from the work done in conjunction with the KU ADC for her summer research experience presentation as part of the Neurological and Rehabilitation Sciences Training Program led by Randolph Nudo, Ph.D. when she noticed a key piece to the puzzle. Rather than examining the resting data and then the steady-state data at the end of the exercise period, perhaps they needed to use data captured by the TCD to look at the subject's response on a continuum from rest to exercise.
"Certainly Sarah had a big role," Billinger said. "It was her question that made me take pause and say 'We're really missing a piece here. Her looking at the data in a new way and asking that question has really changed the way we're looking at brain blood flow."
Billinger said this notion of continuously monitoring cerebral blood flow using TCD resulted in a paradigm shift in her thinking.
Searching for similar testing procedures, Billinger reached for a textbook in her office that characterized muscle blood flow continuously in the forearm from rest to specified exercise intensity. Prior to this, researchers tracking cerebral blood flow in the brain had primarily used devices such as MRIs that require subjects to remain still, thus limiting the process to checking participants only at rest or after exercise.
As Billinger's team looked through the literature, they noticed that no one had characterized the continuous response in the middle cerebral artery (MCA), looking at a person's resting values; through the beginning of exercise; and up to a steady-state heart rate. Billinger wasn't sure it could be done, or that the results would have meaning.
After months of perfecting the technique and developing a rigorous, well-controlled experimental protocol, they were ready to obtain an expert opinion. Billinger invited one of her mentors, David Poole, Ph.D., D.Sc., co-director of the Cardiorespiratory Laboratory at Kansas State University, to come examine the data. Poole, who has built a career on oxygen-uptake dynamics and authored the textbook Billinger referenced, traveled to the KU Medical Center campus to help Billinger's team model the dynamic cerebral artery response from rest to exercise.
To test their hypothesis, Billinger's team and Poole investigated the dynamic cerebral artery response in eight healthy young adults, three older adults and one person who had experienced a stroke as part of study conducted in the REACH Lab. As a result, Billinger's team and Poole were the first in the world to publish the methodology for modeling the dynamic response of the MCA to moderate-intensity exercise.
"What we found is that the young, healthy people respond more quickly and have a higher amplitude," Billinger said. "In the older adults, the response is blunted and we don't know if that is due to aging or other factors. The stroke patient did not have much of a response at all.
"A cardiac stress test examines how the heart responds to exercise, so we may have the beginning of an exercise stress test for the brain," she continued. "We see differences between young and older adults for the dynamic MCA response. We even see differences in the stroke affected MCA when compared to the non-stroke affected artery. I believe our methodology and experimental protocol will provide unique evidence around cerebrovascular health and what we need to do to maintain brain health. I think that will be very valuable to the scientific and medical communities."
So now that they have a proven method for modeling cerebral blood flow in a dynamic situation, questions abound about how best to use the information. Questions such as: What are the consequences of reduced brain blood flow? Are there markers that medical professionals can use to assess brain health and natural brain aging?
"Certainly there is potential for research, especially in various applications for people with chronic diseases or for understanding the aging process," Billinger said. "With the emphasis on brain aging around the globe, I think looking for biomarkers of brain health and using non-invasive methods such as this are an excellent opportunity for future exploration.
"I think there are some exciting next steps," she continued. "I see potential applications for stroke research and recovery. There is no information on how the cerebrovascular system responds during exercise in people with neurologic injury such as stroke. Another area that our work could have an effect on might be concussions/head injuries with implications for return to play/sport. Research has shown repeated concussions have a negative impact on brain health, so hopefully we can explore this uncharted area of research as well."
The options for future study seem endless. Billinger's team is already creating a database to help understand brain blood flow across risk factors, including age, physical activity and cardiovascular risk. And the study published in conjunction with the KU ADC that looked at cognitively normal adults with varying risks of Alzheimer's disease has piqued the team's interest into taking a closer look at the brains of people who are predisposed to dementia and lower cognitive function.
"Our study involved looking at the presence of beta amyloid,' Billinger said. "Because you do see a lower response in people with amyloid, I think tracking the ones with the lowest response to see if they transition into mild cognitive impairment or Alzheimer's disease down the road would be interesting."
Billinger says her team is working diligently to unlock some of the questions and provide new insights into how vascular risk may play a role in brain aging. A research paper, to be submitted soon, describes the role of cardiac risk factors on measures of brain blood flow at rest and during exercise.
As a result of the novel papers Billinger's team has published recently, there has been great interest worldwide in this new method for modeling brain health. Researchers have reached out to learn more about using TCD and the "brain exercise stress test." Billinger spoke last fall at conferences in Hong Kong, Australia and New Zealand, and she has been invited to speak this spring in Singapore.
To be part of the Assessing Cerebral Brain Blood Flow and Transcranial Ultrasound (ACERT) Database, contact the REACH Lab at firstname.lastname@example.org. To qualify for the database you must:
· Be a healthy individual between 20 and 85
· Be willing to visit the REACH Lab at KU Medical Center for about two hours for testing
· Be willing to exercise at three intensities